Day: November 28, 2022

Ren, Long published the artcileCarboxylic Acid-Promoted Single-Step Indole Construction from Simple Anilines and Ketones via Aerobic Cross-Dehydrogenative Coupling, Related Products of indole-building-block, the publication is Journal of Organic Chemistry (2018), 83(23), 14472-14488, database is CAplus and MEDLINE.

The cross-dehydrogenative coupling (CDC) reaction is an efficient strategy for indole synthesis. However, most CDC methods require special substrates, and the presence of inherent groups limits the versatility for further transformation. A carboxylic acid-promoted aerobic catalytic system is developed herein for a single-step synthesis of indoles from simple anilines and ketones. This versatile system is featured by the broad substrate scope and the use of ambient oxygen as an oxidant and is convenient and economical for both laboratory and industry applications. The existence of the labile hydrogen at C-3 and the highly transformable carbonyl at C-2 makes the indoles versatile building blocks for organic synthesis in different contexts. Computational studies based on the d. functional theory (DFT) suggest that the rate-determining step is carboxylic acid-assisted condensation of the substrates, rather than the functionalization of aryl C-H. Accordingly, a pathway via imine intermediates is deemed to be the preferred mechanism. In contrast to the general deduction, the in situ formed imine, instead of its enamine isomer, is believed to be involved in the first ligand exchange and later carbopalladation of the α-Me, which shed new light on this indolization mechanism.

Journal of Organic Chemistry published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, Related Products of indole-building-block.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Isojima, Yasushi published the artcileCkIε/δ-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock, HPLC of Formula: 330161-87-0, the publication is Proceedings of the National Academy of Sciences of the United States of America (2009), 106(37), 15744-15749, S15744/1-S15744/74, database is CAplus and MEDLINE.

A striking feature of the circadian clock is its flexible yet robust response to various environmental conditions. To analyze the biochem. processes underlying this flexible-yet-robust characteristic, we examined the effects of 1260 pharmacol. active compounds in mouse and human clock cell lines. Compounds that markedly (>10 s.d.) lengthened the period in both cell lines, also lengthened it in-central clock tissues and peripheral clock cells. Most compounds inhibited casein kinase Iε (CKIε) or CKIδ phosphorylation of the PER2 protein. Manipulation of CKIε/δ-dependent phosphorylation by these compounds lengthened the period of the mammalian clock from circadian (24 h) to circabidian (48 h), revealing its high sensitivity to chem. perturbation. The degradation rate of PER2, which is regulated by CKIε/δ-dependent phosphorylation, was temperature-insensitive in living clock cells, yet sensitive to chem. perturbations. This temperature-insensitivity was preserved in the CKIε/δ-dependent phosphorylation of a synthetic peptide in vitro. Thus, CKIε/δ-dependent phosphorylation is likely a temperature-insensitive period-determining process in the mammalian circadian clock.

Proceedings of the National Academy of Sciences of the United States of America published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, HPLC of Formula: 330161-87-0.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Abe, Yuichi published the artcileDeep Phospho- and Phosphotyrosine Proteomics Identified Active Kinases and Phosphorylation Networks in Colorectal Cancer Cell Lines Resistant to Cetuximab, Formula: C19H21N3O3S, the publication is Scientific Reports (2017), 7(1), 1-12, database is CAplus and MEDLINE.

Abnormality in cellular phosphorylation is closely related to oncogenesis. Thus, kinase inhibitors, especially tyrosine kinase inhibitors (TKIs), have been developed as anti-cancer drugs. Genomic analyses have been used in research on TKI sensitivity, but some types of TKI resistance have been unclassifiable by genomic data. Therefore, global proteomic anal., especially phosphotyrosine (pY) proteomic anal., could contribute to predict TKI sensitivity and overcome TKI-resistant cancer. In this study, we conducted deep phosphoproteomic anal. to select active kinase candidates in colorectal cancer intrinsically resistant to Cetuximab. The deep phosphoproteomic data were obtained by performing immobilized metal-ion affinity chromatog.-based phosphoproteomic and highly sensitive pY proteomic analyses. Comparison between sensitive (LIM1215 and DLD1) and resistant cell lines (HCT116 and HT29) revealed active kinase candidates in the latter, most of which were identified by pY proteomic anal. Remarkably, genomic mutations were not assigned in most of these kinases. Phosphorylation-based signaling network anal. of the active kinase candidates indicated that SRC-PRKCD cascade was constitutively activated in HCT116 cells. Treatment with an SRC inhibitor significantly inhibited proliferation of HCT116 cells. In summary, our results based on deep phosphoproteomic data led us to propose novel therapeutic targets against cetuximab resistance and showed the potential for anti-cancer therapy.

Scientific Reports published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Formula: C19H21N3O3S.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Chin, Chen-Ni published the artcileThe third transmembrane helix of the cannabinoid receptor plays a role in the selectivity of aminoalkylindoles for CB2, peripheral cannabinoid receptor, Name: 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, the publication is Journal of Pharmacology and Experimental Therapeutics (1999), 291(2), 837-844, database is CAplus and MEDLINE.

Two subtypes of the human cannabinoid receptor have been identified. The CB1 receptor is primarily distributed in the central nervous system, whereas the CB2 receptor is associated with peripheral tissue, including the spleen. These two subtypes are also distinguished by their ligand-binding profiles. The goal of this study was to identify critical residues in transmembrane region III (TM3) of the receptors that contribute to subtype specificity in ligand binding. For this purpose, a chimeric cannabinoid receptor [CB1/2(TM3)] was generated in which the TM3 of CB1 was replaced with the corresponding region of CB2. These receptors were stably expressed in Chinese hamster ovary cells for evaluation. The binding affinities of CB1/2(TM3) and the wild-type CB1 receptor to several prototype ligands were similar with one notable exception: the chimeric receptor exhibited a 4-fold enhancement in binding affinity to WIN 55212-2 (K_d = 4.8 nM) relative to that observed with CB1 (K_d = 21.7 nM). Two addnl. aminoalkylindoles, JWH 015 and JWH 018, also bound the chimeric receptor (K_i = 1.0 μM and 1.4 nM, resp.) with higher affinity compared with the wild-type CB1 (K_i = 5.2 μM and 9.8 nM, resp.). Furthermore, the increase in binding affinities of the aminoalkylindoles were reflected in the EC₅₀ values for the ligand-induced inhibition of intracellular cAMP levels mediated by the chimeric receptor. This pattern mirrors the selectivity of WIN 55212-2 binding to CB2 compared with CB1. Site-specific mutagenesis of the most notable amino acid changes in the chimeric receptor, Gly195 to Ser and Ala198 to Met, revealed that the enhancement in WIN 55212-2 binding is contributed to by the Ser but not by the Met residue. The data indicate that the amino acid differences in TM3 between CB1 and CB2 play a critical role in subtype selectivity for this class of compounds

Journal of Pharmacology and Experimental Therapeutics published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C23H23ClN2O4, Name: 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Ishii, Hisashi published the artcileFischer indolization and its related compounds. V. Indolization of ethyl pyruvate 2-methoxyphenylhydrazone and its N-methyl derivative with protic acids. Unpredictable products and the mechanism, Formula: C12H13NO3, the publication is Chemical & Pharmaceutical Bulletin (1973), 21(7), 1481-94, database is CAplus.

Fischer indolization of Et pyruvate 2-methoxyphenylhydrazone (I) and its N-Me derivative with protic acids gives mainly 6-substituted indole derivatives formed by substitution of the MeO group of I with nucleophiles in the reaction medium. The mechanism involved the cation II as the key intermediate in the formation of the unexpected indole products.

Chemical & Pharmaceutical Bulletin published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, Formula: C12H13NO3.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Ishii, Hisashi published the artcileFischer indolization and its related compounds. VI. Effect of reagents and substituent of the o-substituted phenylhydrazone on abnormal Fischer indolization, COA of Formula: C12H13NO3, the publication is Chemical & Pharmaceutical Bulletin (1973), 21(7), 1495-505, database is CAplus.

Treatment of Et pyruvate 2-methoxyphenylhydrazone (I) with Lewis acid gave 5-substituted and/or 5-methoxyindoles with Et 7-methoxy-indole-2-carboxylate as the main product in contrast with the abnormal Fischer indolization of I. Differences of the acid strength of the reagent and of the electron d. on a benzene ring due to introduction of some other addnl. substituents was the determinant for the abnormal transformation.

Chemical & Pharmaceutical Bulletin published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, COA of Formula: C12H13NO3.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Ishii, Hisashi published the artcileSubstitution and migration of methoxyl group in the Fischer indolization of ethyl pyruvate 2-methoxyphenylhydrazone, Computed Properties of 20538-12-9, the publication is Tetrahedron Letters (1970), 1181-4, database is CAplus.

The indolization of 2-MeOC6H4NHN:CMeCO2Et (I) with 3M HCl-EtOH gave Et 6-chloroindole-2-carboxylate, Et 7-methoxyindole-2-carboxylate (II), and Et 6-ethoxyindole-2-carboxylate. The treatment of I with BF3 in AcOH or AcOEt gave IIk, Et indole-2-carboxylate (III), and Et 5-methoxyindole-2-carboxylate (IV). The treatment of I with H2SO4, in AcOH gave II, III, and IV. A mechanism involving substitution and migration of the MeO group is discussed.

Tetrahedron Letters published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, Computed Properties of 20538-12-9.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Ishii, Hisashi published the artcileFischer indolization and its related compounds. XIII. Measurement of the nuclear magnetic resonance spectra of ethyl indole-2-carboxylate derivatives using the shift reagent and its application, Name: Ethyl 7-methoxy-1H-indole-2-carboxylate, the publication is Yakugaku Zasshi (1979), 99(4), 413-20, database is CAplus and MEDLINE.

Proton NMR spectra of several Et indole-2-carboxylate derivatives in the presence of a shift reagent, tris(dipivalomethanato)-europium [Eu(DPM)₃], were measured in CDCl₃ and good straight lines were obtained on plotting induced shift vs. concentration of Eu(DPM)₃ for each signal. Application of the McConnell-Robertson equation to interpret pseudocontact shifts of the indole derivatives gave good agreement between measured and predicted shifts. The relation between substituents of indoles and the position of the coordinated Eu atom is discussed.

Yakugaku Zasshi published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, Name: Ethyl 7-methoxy-1H-indole-2-carboxylate.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Ishii, Hisashi published the artcileFischer indolization and its related compounds. VIII. Formation of 4-aminoindole derivatives on the Fischer indolization of 2-methoxyphenylhydrazone derivatives, Recommanded Product: Ethyl 7-methoxy-1H-indole-2-carboxylate, the publication is Chemical & Pharmaceutical Bulletin (1974), 22(9), 1981-9, database is CAplus.

Fischer indolization of Et pyruvate 5-chloro-2-methoxyphenylhydrazone with ZnCl2 gave Et 4-amino-6-chloroindole-2-carboxylate (I,R = 4-NH2R1 = 6-Cl) together with I (R = 5-Cl, 5-OMe, R1 = 6-Cl; R = 4-Cl, R1 =7-OMe). Cyclization of Et Pyruvate 2-methoxyphenylhydraxone with p-toluenesulfonic acid in the presence of malonate gave Et 4-(ethoxycarbonylacetamido)indole-2-carboxylate and di-Et 4-(ethoxycarbonylacetamido)-3,6′-biindole-2,2-dicarboxylate with I (R = H, R1 = 5-OMe, 7-OMe,5-O3SC6H4Me-p) and aminoindole product in the abnormal Fisher indolization of a 2-methoxyphenylhydrazone derivative is discussed.

Chemical & Pharmaceutical Bulletin published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, Recommanded Product: Ethyl 7-methoxy-1H-indole-2-carboxylate.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Ishii, Hisashi published the artcileAbnormal Fischer indolization and its related compounds. XII. Synthesis of 3,6′-biindole, Application In Synthesis of 20538-12-9, the publication is Chemical & Pharmaceutical Bulletin (1979), 27(2), 346-50, database is CAplus.

Fisher indole reaction of Et indole-2-carboxylate with (E)-2-MeOC₆H₄NHN:CMeCO₂Et (I) in refluxing C₆H₆ containing MeC₆H₄SO₃H gave 12.2% Et 7-methoxyindole-2-carboxylate and 28.4% biindole II (R = CO₂Et). Saponification of II (R = CO₂Et) gave II (R = CO₂H) which was decarboxylated by heating in quinoline containing Cu-chromite to give 3,6′-diindole (II; R = H). Treatment of indole with I in refluxing C₆H₆ containing MeC₆H₄SO₃H gave 11.3% Z–I, 25.6% diindolylpropionate III, and 17.3% indole trimer IV.

Chemical & Pharmaceutical Bulletin published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, Application In Synthesis of 20538-12-9.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles